Malformations of cortical development

Gene: TMEM161B

I don't know

PMID: 36669111 describes 3 families with either homozygous or compound heterozygous for variants in TMEM161B. Variants described in the article are missense or splice site (splice site was shown in PMID 38593811 to result in skipping of exon 8 which resulted in an removal of the 'most highly conserved portion of the protein'). Article also generated and describe TMEM161B null mice which broadly phenocopy the clinical indications described in the 3 families (null mice show holoprosencephaly, craniofacial midline defects, eye defects, and spinal cord patterning changes) ; there is a suggestion that TMEM161B interacts with SHH but within the CNS. Data is supported by gnomAD - within MANE select there are no homozygous LOF variants recorded; only LOF variant present in the homozygous state occurs downstream of the MANE select (in TMEM161-213).

Created: 3 Sep 2026, 10:26 a.m. | Last Modified: 3 Sep 2026, 10:26 a.m.

Panel Version: 8.11

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Polymicrogyria

Publications

• 36669111
• 38593811
• 37486637